tbuckley/cabot-search huggingface dataset:
Racial disparities in surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing pancreas surgery.
Authors: Mariam Saad, Kendyll Gartrelle, Rupen A. Shah, Julie Clark, Christopher P. Steffes, David S. Kwon
Journal: Journal of Clinical Oncology (2022)

e16255 Background: Previous studies have suggested disparity in PDAC survival in African American (AA) compared to non-AA patients. Pancreas surgery is associated with significant morbidity, and technical outcomes are known to impact survival; however, there is little reported data on surgical outcomes by race. We sought to evaluate the effect of race on surgical outcomes and survival in an urban tertiary care center for patients with PDAC undergoing pancreas surgery. Methods: A retrospective single-center analysis of PDAC patients undergoing pancreas resection between January 2013 and September 2021 was performed. Patient demographics, Clavien-Dindo (CD) complications, readmission, and mortality in the 30- and 90- day period were collected and stratified by race. Univariate and multivariate analyses were performed. Results: Among 180 patients, 145 (81%) were non-AA and 35 (19%) were AA. Demographic and pre-operative characteristics were found to be similar between the two groups. 30-day ED visits, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and intra-abdominal abscess (IAA) were found to be significant on univariate analysis in the AA cohort. On multivariate analysis, 30-day ED visit (OR 4.5; 95% CI 1.3-15.8; p = 0.02), POPF (OR 4.5; 95% CI 1.3-14.8; p = 0.015), and IAA (OR 4.4; 95% CI 1.12-17.3; p = 0.033) were still significantly higher in the AA cohort while DGE lost its significance. Median overall survival and disease-free survival showed no significant difference on Kaplan-Meier curves. There was no statistical difference in local, regional, or metastatic recurrence patterns between the two groups (distant metastasis 36% in non-AA and 37% in AA). Conclusions: AA undergoing pancreas surgery for PDAC were noted to have higher incidence of POPF and IAA as well as ED visits compared to non-AA patients. However, no significant difference was seen in reoperation rates, major CD complications, recurrences, or survival. Exploring tumor biology, and preoperative treatment algorithms may shed additional insight on the differences in surgical outcomes in this patient cohort.[Table: see text]
NURS-01. Development and Implementation of a MEK Inhibitor Targeted Therapy Standardized Educational Curriculum for Pediatric Oncology Patients, Caregivers, and Clinical Staff
Authors: Kasey Rangan, Kimberly Bira, Lauren Bryant, Kaaren Waters
Journal: Neuro-Oncology (2022)

Abstract Molecular targeted therapies have become a fundamental treatment regimen within pediatric oncology practice, yet these medications are not without side effects, which often require interruption, dose reduction, or early discontinuation of treatment. Existing chemotherapy education curriculums focus on the side effect profile of traditional chemotherapy regimens and do not include standardized instruction on toxicities related to targeted therapies, resulting in a knowledge gap for caregivers and the clinical team. The purpose of this project was to development and implement a standardized teaching curriculum to educate patients, caregivers and clinical staff on common toxicities related to MEK inhibitors including anticipated side effects, symptom management, and toxicity surveillance. The education was presented to patients and families by a neuro-oncology nurse or nurse practitioner at the initiation of MEK inhibitor therapy. The cohort consisted of 11 patients over a 12-month period with a diagnosis of plexiform neurofibromas and neurofibromatosis type 1. Additionally, the education curriculum was presented to clinical staff during an in-service and included a pre-post intervention survey to assess effectiveness of the education curriculum. The results demonstrated that increasing patient and family knowledge at initiation of MEK inhibitor therapy likely leads to fewer dose reductions, drug interruptions, and early therapy discontinuations. Greater than 90% of the patient cohort were able to complete the treatment regimen without early termination due to toxicity, with only 18% requiring dose reduction and 9% requiring interruption of therapy. Surveys evaluating the effectiveness of the staff educational curriculum demonstrated an increased knowledge in the identification and treatment of MEK inhibitor side effects with a 26% improvement in survey results post-intervention. This project is a feasible educational approach for preventing and treating toxicities associated with MEK inhibitors and can be initiated at pediatric oncology practices to standardize MEK inhibitor education to clinicians, patients, and caregivers.
Analysis of US Household Catastrophic Health Care Expenditures Associated With Chronic Disease, 2008-2018
Authors: Young-Rock Hong, Zhigang Xie, Ryan Suk, Amir Alishahi Tabriz, Kea Turner, Peihua Qiu
Journal: JAMA Network Open (2022)

0.5%; P = .02)households with members with multimorbidity had significantly decreased prevalence of CHCEs.
Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.
Authors: Thomas Matoska, Lauren Jurkowski, Anjishnu Banerjee, Aditya V. Shreenivas, Monica Shukla, Enrique Martinez, Divya Kodali, Paul Linsky, Mario Gasparri, Sakti Chakrabarti, Ben George, Elizabeth Gore, Candice Aitken Johnstone, David Johnstone, Lindsay Puckett
Journal: Journal of Clinical Oncology (2022)

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8 th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]
Combination of donafenib and anti-PD-1 antibody plus trans-arterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (uHCC).
Authors: Shanzhi Gu, Yulin Tan, Huan Zhou, Hongtao Hu, Tongsen Zheng, Zhendong Zheng, Xu Zhu, Mu Yuan
Journal: Journal of Clinical Oncology (2022)

e16197 Background: Donafenib (Dona), a multikinase inhibitor recently marketed in China for advanced HCC with its superiority in overall survival (OS) over Sorafenib from a large head-to-head Phase 3 study. The clinical experience of triple therapy (TKIs + ICIs + TACE) in the treatment of patients (pts) with uHCC is limited. We assessed the safety and efficacy of triple therapy [Dona +anti-PD-1+ TACE] in uHCC in this Phase 1 study. Methods: The objective of this Phase 1, open-label, multicenter, dose-escalation and expansion study was to assess the MTD/recommended dose for Dona in combination of a fixed-dose anti-PD-1 plus TACE in uHCC. The primary endpoint was DLT occurring in the first treatment cycle. Secondary endpoints included the overall safety and tolerability, ORR and PFS by mRECIST. Qualified pts (age 18-75) were enrolled if uHCC without macrovascular invasion (VP3/4) or extrahepatic spread; measurable disease by mRECIST; ECOG 0 to 1; Child-Pugh A; systemic therapy naive. Results: At the cut-off date (Dec 31 2021), data of 25 pts who underwent triple therapy from 6 cancer centers in China were analyzed (Table). The median duration of follow-up was 105 days (1-358 days). No DLTs were observed [Dona 50 mg Bid (n=3); 150 mg Qd (n=3); 100 mg Bid (n=6)]. Additional 13 pts were treated with the recommended dose of Dona 100 mg Bid. Treatment-related adverse events (TRAE) occurred in 24 pts (Grade 3, 36%; no Grade 4). 16 pts had at least one response assessment, the ORR was 62.5%; in 12 pts with BLCL B, the ORR was 83.3%. mPFS was not reached. Conclusions: Combination of Dona, anti-PD-1 and TACE showed a high rate of tumor response and good safety profile in uHCC. Clinical trial information: NCT04605185. [Table: see text]
Monitoring and management of interstitial lung disease/pneumonitis among patients with metastatic breast cancer treated with trastuzumab deruxtecan.
Authors: Jonathan K. Kish, Sandhya Mehta, Jackie Kwong, Clara Lam, Angelica Falkenstein, Cherrishe Brown-Bickerstaff, Dong Xiao, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2022)

1036 Background: Trastuzumab Deruxtecan (T-DXd) was associated with an increased risk of interstitial lung disease (ILD)/pneumonitis (P) in metastatic breast cancer (mBC) patients (pts) in clinical trials, leading to ILD/P monitoring and management guidelines in the product label. This study aims to describe the monitoring and management of ILD/P during T-DXd therapy among US community oncology practices. Methods: Oncologists in the Cardinal Health Oncology Provider Extended Network (OPEN) participated in a cross-sectional survey on monitoring approaches for ILD/P among mBC pts. Participating physicians provided data from medical charts of up to 10 pts who were treated with T-DXd regarding presence of ILD/P symptoms, management, and outcomes of ILD/P symptoms. Results: Twenty-eight physicians from across the U.S participated and provided data on 149 T-DXd pts. Nearly all physicians reported they were monitoring ILD/P after T-DXd initiation by physical examination (n = 27), symptoms checklist (n = 25) and pulse oximetry (n = 23) at every visit, whereas fewer reported performing lung CT scan (n = 18), echocardiogram (n = 13), chest X-ray (n = 12), lung PET scan (n = 10), pulmonary function tests (n = 8) and diffusion testing (n = 7) on a less frequent basis. Among 149 T-DXd pts, 4 pts were diagnosed with ILD/P over an average T-DXd treatment duration of 5.5 months. All 4 cases initiated T-DXd treatment at 5.4mg/kg every 3 weeks, experienced ILD/P within the first 5 cycles of T-DXd, were diagnosed with lung CT scan and initially presented with Grade 2 symptomology (2 cases progressed to Grade 3). For both cases that remained as Grade 2, ILD/P completely resolved within 23 days. One case received IV methylprednisolone (1000mg daily; duration of therapy (DOT): 3 days) during hospitalization, oxygen therapy and T-DXd was permanently discontinued; whereas the other one received oral prednisone (started at 40mg daily and tapered to 5mg daily; DOT: 7 days) and T-DXd dose was held. For the two grade 3 cases, one received IV methylprednisolone (125mg daily; DOT: 7 days) during hospitalization, T-DXd dose was held, and ILD/P completely resolved within 11 days; whereas the other case received oral prednisone (started at 80mg daily and tapered to 5mg daily; DOT: 63 days), oxygen therapy, T-DXd was permanently discontinued, and ILD/P resolved with sequela within 46 days. Conclusions: ILD/P incidence in this small study sample of patients receiving T-DXd treatment was 2.7%. Although general awareness of ILD and routine screening by pulse oximetry and physical exam were common, management approaches for ILD/P were not always consistent with T-DXd prescribing information. Further physician education may be needed to improve appropriate management of ILD/P and outcomes for T-DXd pts.
Modelling treatment benefit for bexmarilimab (an anti-Clever-1 antibody and a novel macrophage reprogrammer) using phase I/II first-in-man trial data.
Authors: Petri Bono, Jussi Ekström, Marie-Louise Fjällskog, Juho Jalkanen, Teppo Huttunen, Jussi Koivunen
Journal: Journal of Clinical Oncology (2022)

e14500 Background: Bexmarilimab, an investigational immunotherapeutic antibody targeting Clever-1, is currently investigated in phase I/II MATINS study (NCT03733990) for advanced solid tumors. Machine learning (ML) based models combining extensive data could be generated to predict treatment responses to this first-in-class macrophage checkpoint inhibitor. Methods: 52 baseline features from 138 patients included in the part 1/2 of phase I/II MATINS trial were included in ML modelling. 19 patients were classified as benefitting from the therapy by RECIST 1.1 defined clinical benefit rate (DCR) at cycle 4. Initial feature selection was done using both domain knowledge and removal of features with several missing values resulting in 44 features from 102 patients. The remaining data was standardized and feature selection using variance analysis (ANOVA) based on F-values between response and features was performed. With this approach, and by removing features with high multicollinearity, the number of features could be further reduced, and used sample size increased by removing features with missing values, until only the most important features were included in the data. Feature selection resulted in nine baseline features from 127 patients, of which 18 with DCR, to be used for ML model selection and training Several ML models were trained, and prediction performance evaluated using leave-one-out cross-validation (LOOCV). In LOOCV a ML model is trained as many times as there are samples in the data (127 times in this case), each time leaving one sample out from the training set as a test set. Finally, the out-of-sample test results are aggregated to form an overall view of the model performance with unseen data. Regularized Extreme gradient boosting (XGBoost) was found out to be the best performing prediction model. Results: Nine baseline features were associated with bexmarilimab treatment benefit, and the best ML prediction performance was obtained with five features. CBR was associated with low TNFalpha and neutrophils, and high Eotaxin, CK, and T-regs. ML model trained with these five features performed well in LOOCV as 15/18 (83%) DCR and 101/109 (93%) non-DCR were classified correctly, and all considered classification performance metrics were excellent. In feature importance analysis, high baseline T-regs and Eotaxin, and low TNFalpha were characterized as the most important predictors for treatment benefit with relative importances of 0.34, 0.25, and 0.24 (out of 1). Conclusions: This study highlights possibility of using ML models in predicting treatment benefit for novel cancer drugs such as bexmarilimab and boost the clinical development. The findings are in line with expected novel immune activating mode-of-action of bexmarilimab. Clinical trial information: NCT03733990.
EVOKE-01: A phase 3 study of sacituzumab govitecan (SG) versus docetaxel in patients with non–small cell lung cancer (NSCLC) progressing on or after platinum-based chemotherapy and checkpoint inhibitors.
Authors: Marina Chiara Garassino, Douglas Reznick, Steven Y. Liu, Niels Reinmuth, Nicolas Girard, Filippo de Marinis, Sabeen Fatima Mekan, Riddhi Patel, Michelle Ding, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2022)

TPS9149 Background: Single-agent chemotherapy, such as docetaxel, is the standard of care in patients with metastatic NSCLC who progressed on platinum-based therapy and checkpoint inhibitors. However, docetaxel is associated with poor survival (median overall survival [OS] of &lt; 1 year); thus, novel agents are needed to further improve outcomes in this setting. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. In a single-arm expansion of the phase 1/2 IMMU-132-01 basket study of advanced epithelial cancers (NCT01631552), SG demonstrated an objective response rate (ORR) of 17% and median OS of 9.5 months, with a manageable safety profile in 54 patients with metastatic NSCLC who had multiple prior therapies (Heist RS, et al. J Clin Oncol. 2017). EVOKE-01 randomized phase 3 study was designed to further evaluate SG in patients with metastatic NSCLC. Methods: EVOKE-01 (NCT05089734) is an open-label, global, multicenter, randomized, phase 3 study comparing the efficacy and safety of SG vs docetaxel in patients with metastatic NSCLC. Key eligibility criteria include age ≥18 years, pathologically documented stage IV NSCLC at time of study entry, and progression after platinum-based chemotherapy and anti-PD(L)1 therapy given either in combination or sequentially. Patients with EGFR, ALK, or other known actionable genomic alterations must have also received treatment with ≥1 approved appropriate TKI. Other inclusion criteria are ECOG performance status 0-1 and adequate hematologic, hepatic, and renal function. Patients with prior treatment with topoisomerase inhibitors are excluded. Patients are randomized 1:1 to receive intravenous SG (10 mg/kg on day 1 and 8) or docetaxel (75 mg/m 2 on day 1) in 21-day cycles until progressive disease or unacceptable toxicity. Stratification is based on predominant histology (squamous vs nonsquamous), best response to prior immune therapy (PD/SD vs CR/PR), and prior therapy for actionable genomic alteration (yes vs no). The primary endpoint is OS. Key secondary endpoints include progression-free survival, ORR, duration of response, and disease control rate, as assessed by investigator RECIST v1.1, mean change from baseline in NSCLC-SAQ total score and shortness of breath, and safety. This study plans to enroll ̃520 patients globally and is open for recruitment. Clinical trial information: NCT05089734.
National trends in incidence of prostate cancer by age, ethnicity, region, and rurality from 2000-2018: An analysis of US NPCR Database.
Authors: Eashwar Somasundaram, Jacob Lang, Sree Jambunathan, Mersiha Hadziahmetovic, Oluchi Ukaegbu Oke, Firas G. Petros, Obi Ekwenna
Journal: Journal of Clinical Oncology (2022)

e17054 Background: Prostate cancer (PC) is the most common cancer and second leading cause of cancer-related death among males in the United States. Screening recommendations and treatments for PC have changed considerably over the past two decades, with differential effects across sociodemographic groups. This study aims to characterize trends in incidence of PC from 2000 to 2018 by age, race, region, and rurality to better understand these effects on incidence. Methods: Data were obtained from the National Program of Cancer Registries (NPCR), which represents patients for all 50 states. Incidence rates and average annual percent change (AAPC) were calculated using SEER*Stat software. Incident rates were calculated as the number of new cancers arising in the prostate (ICD-O-3 Site Code: C619) per 100,000 males. Trends across sociodemographic groups were analyzed and visualized in R. Results: PC incidence decreased significantly for all ages 40 and above from 2000 to 2018. Ages 85+ experienced the sharpest decline with an AAPC of -5.5% (95% CI: -6.0% to -5.1%). However, for all 5-year age brackets between 60 and 85, incidence reaches a minimum in 2014 before rising again as shown by segmented regression analysis. All race/ethnicity groups experienced a significant decline in incidence from 2000 to 2018 with sharpest decline in Hispanics -3.9% (95% CI: -4.5% to -3.3%). All regions also experienced a significant decline, with the greatest decline in the West at -4.0 (95% CI: -4.7 to -3.3). Metropolitan counties experienced a greater decline than nonmetropolitan. Patients ages 65 to 79, of Black race/ethnicity, and metropolitan groups had the highest overall incidence over the study period in their respective categories with 2018 incidences of 663, 181, and 115 per 100,000 males respectively. Conclusions: Nearly all sociodemographic groups have experienced a decline in the incidence of PC from 2000 to 2018. However, PC incidence increased from 2014 to 2018 for several sociodemographic groups. Importantly, 65 to 79 year olds, Black Americans, and metropolitan groups had the highest incidence over the study period. This study demonstrates a sustained rise in incidence of PC for several sociodemographic groups, as well as identifies groups at higher risk of PC. These trends may be due to evolving PC screening guidelines and merit further investigation.
LINC-23. Factors influencing outcomes of older children with Medulloblastoma over 15 years in Peru, a resource limited setting
Authors: Rosdali Diaz-Coronado, James B Reinecke, Joseph R Stanek, Jonathan L Finlay, Eddy Hernandez-Broncano, Sharon Chavez-Paredes, Yesenia Miranda-Tunque, Adela Heredia-Zelaya, Sandro Casavilca-Zambrano, Pamela Garcia-Corrochano, Luis Ojeda-Medina, Enrique Orrego-Puelles, Ebert Torres-Malca, Raymundo Sernaque-Quintana, William Quispe-Valverde, Juan Garcia-Leon, Diana S Osorio
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with Medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997-2013, data from 103 children older than three years with Medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997 – 2008 and 2009 – 2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, while prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The five-year OS was 62% (95% CI: 53 – 74%) while EFS was 57% (95% CI: 48 – 69%). The variables adversely affecting survival were anaplastic histology [compared to desmoplastic; OS: HR=3.4, p=0.03], metastasis [OS: HR=3.5, p=0.01; EFS: HR=4.3, p=0.004], delay in radiation therapy of 31-60 days [compared to ≤30 days; EFS: HR=2.1, p=0.04], and treatment 2009 – 2013 cohort[OS: HR=2.2, p=0.02; EFS: HR=2.0; p=0.03]. CONCLUSIONS: Outcomes for Medulloblastoma at INEN were low compared with HIC. Anaplastic sub-type, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009 - 2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.